IgG4抗体药物研究进展  

Research Progress of IgG4 and IgG4 Fusion Protein

作　　者：王力景 邢莹莹[1] WANG Li-jing;XING Ying-ying(School of Life Science and Technology,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京211198

出　　处：《药物生物技术》2023年第1期106-110,共5页Pharmaceutical Biotechnology

摘　　要：IgG是人体内最为丰富的抗体类型,也是应用最为广泛的治疗性蛋白药物。IgG共有4种亚型,不同亚型之间结构和性质具有差异。目前IgG1药物的应用与研究最为广泛,其余亚型的研究相对较少。然而,IgG4也有其独特的优势,其主要具有两个特点:一是其几乎不产生免疫效应功能,因此可起到单纯的中和抗体的作用,再加上IgG共有的半衰期较长的性质,可用于与其他蛋白形成融合蛋白以延长半衰期,从而最大限度减少免疫副反应;二是Fab臂交换,可用于形成多特异性抗体。近年来,关于IgG4的研究快速增加,本综述从IgG4的基本结构与性质入手、参考了大量近期发表的相关文献、全面探讨了近几年IgG4药物从药物设计到实际生产再到质量检测等各个方面的研究进展。从中,作者认为IgG4在药物开发中具有较高的潜力。IgG is the most abundant type of antibody in the human body and the most widely used therapeutic protein drug.There are four subtypes of IgG:IgG1,IgG2,IgG3,and IgG4.Their structures and properties are different, and the application and research of IgG1 are the most popular.However, IgG4 contains its unique advantages, which are two main characteristics: first, it has almost no immune effector function so it can play the role of a pure neutralizing antibody, coupled with the long half-life of IgG,it can be fused with other proteins to extend the half-life but hardly elicit immune side reactions;second, the Fab-arm exchange, can be used to form multi-specific antibodies.Currently, research on IgG4 has increased rapidly in recent years.This review starts with the basic structure and properties of IgG4,refers to a large number of recently published relevant literature, and comprehensively discusses the research progress of IgG4 drugs in recent years, from drug design to actual production to quality testing.For example, the influence of glycosylation on conformation and receptor binding was further elucidated, many new types of glycosylation were found;the nature of Fab-arm exchange was found to generate problems in cation exchange chromatography;the mechanism of long effect through neonatal Fc receptor was further clarified;many physicochemical properties, including solubility, viscosity, hydrophobicity, charge, aggregation, chemical stability, and thermal stability, were studied more thoroughly, which are considerably cared by the industrial production;different cell culture methods have different expression yield and quality, and compared to fed-batch culture, perfusion cell culture was proved to be overall better in homogeneity and other parameters;CHO cell line is the most commonly used in expression but it would introduce structural changes;some listed IgG4 drugs were analyzed.Therefore, IgG4 was believed to have a high potential in drug development.

关 键 词：免疫球蛋白4 融合蛋白 半衰期 质量控制 糖基化修饰 酸峰 碱峰 

分 类 号：R614[医药卫生—麻醉学]